Clinical Trial Experience

Adverse event information from clinical trials provides the basis for identifying adverse events that appear to be related to vaccine use and for approximating the rates of these events. However, because clinical trials are conducted under widely varying conditions, adverse event rates observed in the clinical trials of a vaccine cannot be directly compared to rates in the clinical trial of another vaccine, and may not reflect the rates observed in practice.

Adults and Geriatrics

In placebo-controlled studies among adults, the most frequent side effect of vaccination is soreness at the vaccination site (affecting 10%–64% of patients) that lasts < 2 days, local pain and swelling. These local reactions typically are mild. Fever, malaise, myalgia, and other systemic symptoms can occur following vaccination and most often affect persons who have had no prior exposure to the influenza virus antigens in the vaccine (e.g., young children). These reactions begin 6–12 hours after vaccination and can persist for 1–2 days. Placebo-controlled trials demonstrate that among older persons and healthy young adults, administration of split-virus influenza vaccine is not associated with higher rates of systemic symptoms (e.g., fever, malaise, myalgia, and headache) when compared with placebo injections. (2)

Children

The 2003-2004 formulation of Fluzone vaccine was studied in 19 children 6 to 23 months of age and in 12 children 24 to 36 months of age, given in 2 doses one month apart. Local reactions and systemic events were solicited for 3 days after each dose. Most local and systemic reactions were mild. The proportions of local and systemic reactions in children were similar to the proportions in adults. No reported local or systemic reaction required a therapeutic intervention other than analgesics. (3)

Post-Marketing Experience

The following additional events have been reported during post-approval use of Fluzone vaccine. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure.

Other Adverse Events Associated with Influenza Vaccines

Anaphylaxis has been reported after administration of influenza vaccines. Although
Influenza A (H1N1) 2009 Monovalent Vaccine contains only a limited quantity
of egg protein, this protein can induce immediate hypersensitivity reactions
among persons who have severe egg allergy. Allergic reactions include hives,
angioedema, allergic asthma, and systemic anaphylaxis. [See CONTRAINDICATIONS]

The 1976 swine influenza vaccine was associated with an increased frequency of Guillain-Barré syndrome (GBS). Evidence for a causal relation of GBS with subsequent vaccines prepared from other influenza viruses is unclear. If influenza vaccine does pose a risk, it is probably slightly more than 1 additional case/1 million persons vaccinated.